The long term goal of this proposal is to define the pathogenesis of acute, latent and reactivated herpes simplex virus (HSV) infections of the autonomic nervous system. Our principal attention will be directed at: A. The intrinsic properties of autonomic neurons which determine their variable capacity to support either productive or latent HSV infection; B. the cellular metabolic consequences of acute, latent and reactivated HSV infections of the autonomic nervous system. To achieve these objectives 3 experimental systems are being employed: 1) an in vivo model of autonomic infection in the mouse whereby the superior cervical ganglion (SCG) is infected after intraocular viral inoculation; 2) a cell culture model using primary dissociated SCG neurons from newborn rat; and 3) an additional cell culture model using the PC12 pheochromocytoma cell line which undergoes neuron-like differentiation on exposure to nerve growth factor (NGF).